We several projects. 1. A dogma of innate immunity is that neutrophils use chemoattractant GPCRs to chase bacteria through chemotaxis and then use phagocytic receptors coupled with tyrosine kinases to destroy opsonized bacteria via phagocytosis. Our current work has changed this dogma by showing that G-protein-coupled formyl peptide receptors (FPRs) directly mediate neutrophil phagocytosis. Mouse neutrophils lacking formyl peptide receptors (Fpr1/2-/-) are defective in the phagocytosis of E. coli and the chemoattractant fMLP-coated beads. fMLP immobilized on the surface of a bead interacts with FPRs triggers a Ca2+ response, and induces actin polymerization to form a phagocytic cup for engulfment of the bead. Chemoattractant GPCR/Gi signaling and phagocytic receptor/tyrosine kinase signaling work independently to promote phagocytosis of beads coated with either chemoattractants or IgG opsonins. Thus, in addition to phagocytic receptor-mediated phagocytosis, neutrophils also utilize the chemoattractant GPCR/Gi signaling to mediate phagocytosis to fight invading bacteria (Wen etal, in submission). 2. Neutrophils sense and migrate through a large range of chemoattractant gradient through an adaptation mechanism. Here, we reveal CPARI, a negative regulator of Ras, that controls GPCR-stimulated Ras signaling in human neutrophils. Cells lacking CAPRI (caprikd) exhibit significantly increased phosphorylation of AKT, GSK3, and cofilin, leading to excessive actin polymerization and subsequent defects in neutrophil chemotaxis. The caprikd cells display chemotaxis defects only in high concentration, but not in low-concentration gradient, remarkably, show better chemotaxis in sub-responsive concentration of chemoattractant gradient due to their higher sensitivity. Taken together, we reveal that CAPRI controls GPCR-mediated adaptation and downshifts the sensitivity of neutrophils for Chemotaxis.